A wide variety of tests have been developed for the determination of pregnancy. Commercial early pregnancy determinations include the rabbit ovulation test of urine (5.5 wk), rat ovarian hyperemia test of urine (5.5 wk), hemagglutination inhibition latex particle test of urine (5.5 wk), RIA (radioimmunoassay) test of blood using competition with .sup.125 I labeled hCG for anti-(hCG) antibodies (3.5 wk), RIA test of blood using competition with .sup.125 I labeled hCG for anti-(.beta.-hCG) antibodies (3.5 wk), and RRA (radioreceptor assay) test of blood using competition with .sup.125 I labeled hCG for specific receptor sites. The RIA tests have been refined to provide qualitative results the same day but require an additional day to determine the exact titer of hCG or .beta.-hCG in the serum. The RRA assay is more rapid, but is currently less sensitive than the RIA test.
Home pregnancy tests for hCG in urine include a variety of enzyme immunoassays, hemagglutination inhibition, and antibody-antigen agglutination tests which are effective to indicate pregnancy from 0 to 9 days after a missed period. Confirmation by physician is recommended, particularly to determine abnormal gestation such as ectopic pregnancy.
HCG is produced by the fetal trophoblast and passes from the fetal blood into the mother's blood through the intervillous space in the placenta. HCG levels in maternal blood and urine are often detectable at about 3 weeks. The sensitivity of the serum or urine hCG tests is limited because the amount of hCG produced is determined by the amount of trophoblastic tissue, and by the dilution of the hCG in the maternal fluids. Until development of the .beta.-hCG specifically binding antibody, cross-reaction with LH also placed a limit on the level of sensitivity.
We have discovered that normal uterine pregnancies can be determined early in the gestation cycle and with a high reliability by testing a sample for the presence of fetal restricted antigens, that is, antigenic and non-antigenic compounds or materials which are produced in the placental tissue and which do not pass in any substantial amounts into the maternal blood. Included in this class of antigens are fetal fibronectins.